- Structure-activity relationships of 7-substituted dimethyltyrosine-tetrahydroisoquinoline opioid peptidomimetics
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The opioid receptors modulate a variety of biological functions, including pain, mood, and reward. As a result, opioid ligands are being explored as potential therapeutics for a variety of indications. Multifunctional opioid ligands, which act simultaneously at more than one type of opioid receptor, show promise for use in the treatment of addiction, pain, and other conditions. Previously, we reported the creation of bifunctional kappa opioid receptor (KOR) agonist/mu opioid receptor (MOR) partial agonist ligands from the classically delta opioid receptor (DOR) antagonist selective dimethyltyrosine-tetrahydroisoquinoline (Dmt-Tiq) scaffold through the addition of a 7-benzyl pendant on the tetrahydroisoquinoline ring. This study further explores the structure-activity relationships surrounding 7-position pendants on the Dmt-Tiq scaffold. Some analogues maintain a KOR agonist/MOR partial agonist profile, which is being explored in the development of a treatment for cocaine addiction. Others display a MOR agonist/DOR antagonist profile, which has potential to be used in the creation of a less addictive pain medication. Ultimately, we report the synthesis and in vitro evaluation of novel opioid ligands with a variety of multifunctional profiles.
- Montgomery, Deanna,Anand, Jessica P.,Baber, Mason A.,Twarozynski, Jack J.,Hartman, Joshua G.,Delong, Lennon J.,Traynor, John R.,Mosberg, Henry I.
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Read Online
- MACROCYCLIC COMPOUND AND USE THEREOF
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A compound represented by the following formula (I): wherein each symbol in the formula is as described herein or a salt thereof has an NRF2 activating activity, and is expected to be useful as a preventive or therapeutic agent for diseases associated with oxidative stress, in particular, hepatic disease (for example, non-alcoholic steatohepatitis (NASH)), cardiovascular disease (for example, heart failure or pulmonary arterial hypertension), lung disease (for example, chronic obstructive pulmonary disease (COPD)), kidney disease (for example, chronic kidney disease (CKD) or acute kidney injury (AKI)), central nervous system disease (for example, Parkinson's disease), mitochondrial disease (for example, Friedreich motor ataxia, mitochondrial myopathy), inflammatory disease (for example, multiple sclerosis (MS), inflammatory bowel disease (IBD)), sickle cell disease, cancer, or the like.
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Paragraph 0193
(2020/07/05)
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- PYRROLO[2,3-B]PYRIDINES AS HPK1 INHIBITOR AND USES THEREOF
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Disclosed herein is a compound of Formula (I), or a stereoisomer thereof, or a pharmaceutically acceptable salt thereof, and pharmaceutical compositions comprising thereof. Also disclosed is a method of treating HPK1 related disorders or diseases by using the compound disclosed herein.
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Page/Page column 21
(2020/06/10)
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- GPR40 receptor stimulant, and preparation method, pharmaceutical composition and application thereof
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The invention discloses a GPR40 receptor stimulant, and a preparation method, a pharmaceutical composition and application thereof. The invention particularly discloses a GPR40 receptor stimulant shown in general formula (I) and pharmacologically acceptable salt thereof, a preparation process of the compound, a pharmaceutical composition containing the compound of general formula (I), and application of the compound and the pharmaceutical composition in anti-diabetes.
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Paragraph 0163-0165; 0181-0183; 0185
(2019/10/15)
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- NRF2 ACTIVATOR
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Provided are tetrahydroisoquinoline derivatives as Nrf2 activators.
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Page/Page column 45; 46
(2018/08/20)
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- NOVEL TETRAHYDROISOQUINOLINES AND TERAHYDRONAPHTHYRIDINES FOR THE TREATMENT AND PROPHYLAXIS OF HEPATITIS B VIRUS INFECTION
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The present invention provides novel compounds having the general formula (I): wherein R1, R 2, R 3, U, V, W, X and Y are as described herein, compositions including the compounds and methods of using the compounds.
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Page/Page column 41
(2018/05/24)
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- Design, synthesis and biological evaluation of a series of novel GPR40 agonists containing nitrogen heterocyclic rings
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A novel series of GPR40 agonists is designed by introducing nitrogen-containing heterocyclic ring at the terminal phenyl ring of TAK-875 with the aim of decreasing its lipophilicity. Three different β-substituted phenylpropionic acids were investigated as the acidic components. A total of 34 compounds have been synthesized, among which, compound 30 exhibited comparable GPR40 agonistic activity in vitro with TAK-875 and relatively lower lipophilicity through calculation (30, EC50 = 1.2 μM, cLogP = 1.3; TAK-875: EC50 = 5.1 μM, cLogP = 3.4). Moreover, compound 30 was able to enhance the insulin secretion of primary islets isolated from normal ICR mice and showed no obvious inhibition against cytochromes P450 in vitro. In vivo, compound 30 exhibited efficacy in oral glucose tolerance test (oGTT) in normal ICR mice.
- Sun, Zhaozhu,Zhou, Tian,Pan, Xuan,Yang, Ying,Huan, Yi,Xiao, Zhiyan,Shen, Zhufang,Liu, Zhanzhu
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supporting information
p. 3050 - 3056
(2018/08/11)
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- DDQ-promoted mild and efficient metal-free oxidative α-cyanation of N-acyl/sulfonyl 1,2,3,4-tetrahydroisoquinolines
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A mild and highly efficient metal-free oxidative α-cyanation of N-acyl/sulfonyl 1,2,3,4-tetrahydroisoquinolines (THIQs) has been accomplished at an ambient temperature via DDQ oxidation and subsequent trapping of N-acyl/sulfonyl iminium ions with (n-Bu)s
- Kim, Hong Pyo,Yu, Heesun,Kim, Hyoungsu,Kim, Seok-Ho,Lee, Dongjoo
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- Substituted ring compound and its method and use thereof
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The invention provides a substituted cyclic compound as well as a use method and application thereof. The compound is a compound as shown in a formula (I) or stereoisomers, stereomers, tautomers, nitric oxides, solvates, metabolites and pharmaceutically acceptable salts or prodrugs of the compound as shown in the formula (I). The invention further provides a medicament composition containing the compound. The compound and the medicament composition are capable of regulating the activity of protein kinase in a biological sample body and are used for protecting, treating or relieving proliferative diseases of patients. The formula (I) is as shown in the specification.
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Paragraph 0620; 0621
(2017/08/25)
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- ANTIVIRAL COMPOUNDS
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This invention relates to a series of tricyclic compounds comprising a pteridinone core linked to a third heterocycloalkyl ring. The compounds are useful in the treatment of Hepatitis B viral infections. The invention also relates to pharmaceutical compos
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Page/Page column 42-43
(2017/01/23)
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- Of tetracyclic Anaplastic lymphoma kinase inhibitors (by machine translation)
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The invention belongs to the field of medical technology, in particular to general formula (I) as shown in of tetracyclic Anaplastic lymphoma kinase inhibitor, its pharmaceutically acceptable salt or a stereoisomer thereof, wherein R 1, R 2, R 3, R 4, R 5 and A link like defined in the specification. The invention also relates to methods of preparing such compounds, pharmaceutical preparations comprising these compounds and pharmaceutical composition, the compound and, its pharmaceutically acceptable salts or stereoisomers thereof, in the preparation of the treatment and/or prevention of Anaplastic lymphoma kinase-mediated cancer diseases related to the application of the medicament. (by machine translation)
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Paragraph 0274; 0275; 0276
(2016/10/08)
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- SUBSTITUTED CYCLIC COMPOUNDS AND METHODS OF USE
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The present invention provides novel substituted alkynyl compounds, pharmaceutical acceptable salts and formulations thereof useful in modulating the protein tyrosine kinase activity, and in modulating cellular activities such as proliferation, differentiation, apoptosis, migration and invasion. The invention also provides pharmaceutically acceptable compositions comprising such compounds and methods of using the compositions in the treatment of hyperproliferative disorders in mammals, especially humans.
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Paragraph 0240
(2014/06/24)
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- FUSED HETEROCYCLIC COMPOUNDS AS ION CHANNEL MODULATORS
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The present disclosure relates to compounds that are sodium channel inhibitors and to their use in the treatment of various disease states, including cardiovascular diseases and diabetes. In particular embodiments, the structure of the compounds is given
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Page/Page column 115-116
(2012/12/13)
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- SUBSTITUTED HETEROCYCLIC COMPOUNDS
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The present invention relates to substituted heterocyclic compounds of Formula I or XI: or pharmaceutically acceptable salts or N-oxides or quaternary ammonium salts thereof wherein constituent members are provided hereinwith, as well as their compositions and methods of use, which are histamine II4 receptor inhibitors useful in the treatment of histamine II4 receptor-associated conditions or diseases or disorders including, for example, inflammatory diseases or disorders, pruritus, and pain.
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Page/Page column 58
(2010/10/03)
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- 4, 6-DISUBSTITUTED 2-AMINO-PYRIMIDINES AS HISTAMINE H4 RECEPTOR MODULATORS
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The present invention relates to substituted heterocyclic compounds of Formula (I) or pharmaceutically acceptable salts or N-oxides or quaternary ammonium salts thereof wherein constituent members are provided hereinwith, as well as their compositions and methods of use, which are histamine H4 receptor inhibitors/antagonists useful in the treatment of histamine H4 receptor-associated conditions or diseases or disorders including, for example, inflammatory diseases or disorders, pruritus, and pain.
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Page/Page column 94-95
(2010/07/09)
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- PYRIDONE AND PYRIDAZINONE DERIVATIVES AS MCH ANTAGONISTS
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The present invention relates to pyridone and pyridazinone derivatives as listed in claim 1 including their salts. Moreover the invention relates to pharmaceutical compositions containing at least one compound according to the invention. By virtue of thei
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Page/Page column 65
(2009/10/18)
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- CARBON-LINKED TETRAHYDRO-PYRAZOLO-PYRIDINE MODULATORS OF CATHEPSIN S
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Carbon-linked tetrahydro-pyrazolo-pyridine compounds are described, which are useful as cathepsin S modulators. Such compounds may be used in pharmaceutical compositions and methods for the treatment of disease states, disorders, and conditions mediated by cathepsin S activity, such as psoriasis, pain, multiple sclerosis, atherosclerosis, and rheumatoid arthritis.
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Page/Page column 53-54
(2008/12/08)
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- NEW PYRIDONE DERIVATIVES WITH MCH ANTAGONISTIC ACTIVITY AND MEDICAMENTS COMPRISING THESE COMPOUNDS
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The present invention relates to compounds of general formula (I) wherein the groups and radicals B, k, L, U,V, W, X, Y, Z, R1, R2, have the meanings given in claim 1. Moreover the invention relates to pharmaceutical compositions containing at least one compound according to the invention. By virtue of their MCH- receptor antagonistic activity the pharmaceutical compositions according to the invention are suitable for the treatment of metabolic disorders and/or eating disorders, particularly obesity, bulimia, anorexia, hyperphagia and diabetes.
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Page/Page column 82
(2008/06/13)
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- SUBSTITUTED PYRIMIDINES AS ADENOSINE RECEPTOR ANTAGONISTS
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Compounds of formula(I): wherein R1, R2 and R3 are as defined herein, including pharmaceutically acceptable salt, ester, solvate or stereoisomer thereof. Also disclosed are compositions containing a compound of this invention in combination with a pharmaceutically acceptable carrier, as well as methods relating to the use thereof.
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Page/Page column 63
(2008/12/07)
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- INHIBITORS OF FARNESYL-PROTEIN TRANSFERASE
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The present invention is directed to compounds which inhibit farnesyl-protein transferase (FTase) and the farnesylation of the oncogene protein Ras. The invention is further directed to chemotherapeutic compositions containing the compounds of this invention and methods for inhibiting farnesyl-protein transferase and the farnesylation of the oncogene protein Ras
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